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Extra resources for Antiepileptic drugs: combination therapy and interactions
CBZ, LTG, and PHT work at least in part by action at the sodium channel to prevent rapid neuronal firing and seizure spread. VGB or TGB act to increase GABA inhibitory effect and presumably provide different and complementary action. Some support of this concept was reported in the study of Tanganelli and Regestra (1996) in a comparative trial of CBZ or VGB alone or in combination. Although this is a ‘rational’ combination, it implies that we understand the mechanism by which the AEDs work. CBZ and PHT are both thought to function by preventing rapid firing due to action at the sodium channel.
B. Stephens, J. C. C. Talbot, P. A. Routledge, eds. , 1998b. Seymour RM, Routledge PA. Important drug–drug interactions in the elderly. Drug Ageing 1998; 6: 485–494. Shorr RI, Ray WA, Daugherty JR, et al. Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Arch Intern Med 1993; 153(14): 1665–1670. Stephens M. In Detection of New Adverse Reactions, 4th edn. M. D. B. Stephens, J. C. C. Talbot, P. A.
Evidence made clear that the side effect often was due to marked elevation of PB levels as a consequence of inhibition of PB metabolism by VPA rather than a direct effect of VPA. Expense Combinations of AEDs may double the cost of using monotherapy with a few exceptions mentioned above. In some cases combining an enzyme-inducing drug such as PHT with CBZ or VPA increases the clearance, often requiring a much larger dose to achieve blood levels comparable to those achieved with monotherapy. An even greater expense can be incurred by combining one of these older enzymeinducing drugs with one of the costlier new AEDs, LTG, OXC, TPM or ZNS.
Antiepileptic drugs: combination therapy and interactions by Jerzy Majkowski,NetLibrary, Inc.